The success of CTLA-4/PD-1 targeting stimulated explosive growth of Immuno-oncology (IO) agent discovery and development and, as a result, the dramatic increase in possible new combination regimens needing evaluation in people exceeds the capacity of the nation?s trial network to evaluate all of them. Because they resemble human cancers both clinically and biologically, the NCI has decided to explore the use of naturally occurring cancers in dogs as surrogates of human cancers for rapidly evaluating new IO combinations and prioritizing only the most promising ones to advance into humans.. Small, fast Phase 0 canine trials examining the response of molecular biomarkers measured with validated, fit-for-purpose pharmacodynamic (PD) assays should further increase this throughput, analogous to the use of PD biomarkers as endpoints of Phase 0 trials in humans. In order to explore the resemblance in immunotherapy response between human and canine cancers that are MSI-H (a DCTD and COP collaboration), however, a therapeutic monoclonal antibody (MAb) targeting canine CTLA-4 is required. The absence of such a Mab is holding up the clinical evaluation of the benchmark combination regimen in dogs. The NCI has decided to fill this gap immediately by tasking the contractor to create a therapeutic canine monoclonal antibody against CTLA-4 that possesses analogous properties to ipilimumab, its human analog. DCTD will also require the development of validated, fit-for-purpose clinical assays suitable for analyzing PD response and MSI status in canine cancer biopsies. Based on experience with cross-reactivity of diagnostic reagents between human and dog, DCTD estimates that 3-4 of the 8 canine biomarkers will require the creation of new MAb reagents.